International Urology and Nephrology

, Volume 47, Issue 11, pp 1907–1915 | Cite as

Sildenafil activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in a rat model of renal ischemia/reperfusion injury

  • Mohamed H. Zahran
  • Abdelaziz M. Hussein
  • Nashwa Barakat
  • Amira Awadalla
  • Shery Khater
  • Ahmed Harraz
  • Ahmed A. Shokeir
Nephrology - Original article
First Online:
Received:
Accepted:

Abstract

Objectives

To study the possible renoprotective effect of sildenafil against renal ischemia/reperfusion (I/R) injury and its effect on the expression of some antioxidant, antiapoptotic gene and proinflammatory cytokine genes in rat model of renal I/R injury.

Materials and methods

One hundred and twenty male Sprague Dawley rats were subdivided into three equal groups: sham (underwent right nephrectomy without ischemia), control (underwent right nephrectomy and left ischemia for 45 min) and study [as control with 1 mg/kg sildenafil (per oral) 60 min before anesthesia]. Serum creatinine and BUN were measured at the baseline and the study endpoints (2, 24, 48 h and 7 days), and the left kidney was harvested at study endpoints for histopathological examination as well as for assessment of the expression of antioxidant genes (Nrf-2, HO-1 and NQO-1), antiapoptotic gene (Bcl-2) and inflammatory cytokines, e.g., TNF-a, IL-1β and ICAM-1.

Results

I/R caused significant increase in serum creatinine, BUN, histopathological damage score (p < 0.001) and significant reduction in antioxidant genes (nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) with significant increase in TNF-a, IL-1β and ICAM-1 genes in kidney tissues. Pretreatment with sildenafil caused significant attenuation of serum creatinine and BUN as well as significant increase in the expression of antioxidant genes and Bcl-2 genes with significant reduction in the expression of proinflammatory cytokine genes (p value < 0.001).

Conclusion

The renoprotective effect of sildenafil against renal I/R might be due to the activation of antioxidant genes (Nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) and attenuation of proinflammatory cytokines (TNF-a, IL-1β and ICAM-1).

Keywords

Sildenafil Ischemia/reperfusion Kidney Nrf2 HO-1 NQO-1 Bcl-2 
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Notes

Acknowledgments

This work was funded by project # CEP1-031-MANS by ministry of higher education, Egypt.

Compliance with ethical standards

Conflict interest

Authors declare that there is no any conflict of interest.

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Mohamed H. Zahran
    • 1
  • Abdelaziz M. Hussein
    • 2
  • Nashwa Barakat
    • 1
  • Amira Awadalla
    • 1
  • Shery Khater
    • 1
  • Ahmed Harraz
    • 1
  • Ahmed A. Shokeir
    • 1
  1. 1.Urology and Nephrology CenterMansoura UniversityMansouraEgypt
  2. 2.Physiology Department, Faculty of MedicineMansoura UniversityMansouraEgypt

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